Matthew Whited, PhD is a clinical psychologist at the University of Massachusetts Medical School. His long- term goal is to elucidate the mechanisms of the association between depression and cardiovascular disease (CVD) and to identify depression treatments that influence both physical and mental long-term health. Depression is strongly and consistently associated with risk for CVD onset, but the influence of depression treatment on CVD onset is poorly understood. This indicates a need to investigate the effects of the various available depression treatments, and to more thoroughly understand the mechanisms of action by which depression treatments could influence CVD risk. The majority of studies that seek to influence CVD through depression treatment are studies of secondary prevention. This proposal will provide Dr. Whited with the training and mentorship needed to develop expertise in both epidemiological and clinical trials approaches that investigate the effects of depression treatments on primary CVD risk (first CVD event). Two studies are proposed to investigate the effects of each of two types of depression treatment (Selective Serotonin Reuptake Inhibitors: SSRIs and Cognitive Behavioral Therapy: CBT) on CVD risk. Autonomic balance (measured by heart rate variability; HRV) is associated with depression, and is also an established risk factor for CVD; autonomic balance will be the main CVD mechanism of interest in these studies. Study 1 of this proposal will help inform clinical recommendations of SSRI treatment by determining if SSRIs differentially influence primary CVD incidence in patients who are at higher or lower risk for CVD according to a predictive risk score (Framingham Risk Score: FRS). Following this, Heart Rate Variability (HRV) will be examined as a mediator of the SSRI and CVD association. Study 2 is a pilot clinical trial that will reduce depressive symptoms via an evidence-based psychotherapy to observe the effect of depression symptom reduction on HRV in the absence of pharmacotherapy. These studies are linked in that they both investigate the effects of depression treatment on autonomic balance by independently focusing on either antidepressant medications or psychotherapy. Dr. Whited's prior research in psychophysiology complements the training plan, which will provide Dr. Whited with additional knowledge in depression, its treatment, cardiovascular physiology, autonomic imbalance, along with the experience and expertise necessary to study primary CVD risk using epidemiological and clinical trials methodology. His long-term program of research will focus on understanding the influence of depression treatment on primary CVD risk and risk factors in order to inform clinical guidelines for depression treatment based on both physiological and psychological assessment and psychological and physiological treatment targets.